Our major long-term objective is to understand the synaptic connections of the neurons of the human retina that underlie specific visual functions. An understanding of the neural pathways in the normal human retina will give us a basis on which to investigate abnormalities when a disease process has caused loss of, or compromise to, any of the neurons of the retina. Using anatomical techniques of studying serial ultrathin sections and reconstructing neurons that have been electron densely marked by intracellular iontophoresis of HRP or DAB reduction of lucifer yellow stain or labeled by immunostaining, we wish to understand: a) how groups of neurons in particular pathways may be working together as units having input to the ON-center and OFF-center pair of ganglion cells that "see" the same visual space. Where others have been examining horizontally organized mosaics of the same population of neurons we will concentrate on understanding vertically organized units. b) amongst these aims would be looking at how the red/green opponent and the blue/yellow opponent pathways are constructed in their vertical connections, including their surround organization via amacrine cells. c) how the small parasol ganglion cell system is wired, particularly investigating whether diffuse cone bipolar cells and rod amacrine cells are involved. d) We also propose to return to an investigation of cone bipolar cell connectivity to cones both using Golgi-EM techniques, and immunostains such as protein kinase C- beta, recoverin, calbindin and glutamate receptors. c) Finally, we will use in situ hybridization and EM immunocytochemistry in combination to look at chemically different amacrine cell inputs to human and cat amacrine and ganglion cell types. Our studies always incorporate comparisons between cat and human retina and wherever possible we will be studying electrophysiologically recorded and marked neurons of the cat.